These studies are undertaken to study the pathogenesis of the abnormal renal excretion of water in a variety of pathologic states. The renal concentrating defect in hypokalemic and hypercalcemic animals is being investigated with attention to both central (vasopressin release - thirst) and renal (cyclic AMP generation, medullary gradient) mechanisms. The possible role of prostaglandins in these disorders is studied by the use of prostaglandin inhibitors. The abnormal renal dilution associated with congestive heart failure is studied in rats with high cardiac output failure (A-V fistulae). The role of altered systemic hemodynamics, renal hemodynamics, prostaglandins and vasopressin is being delineated. Similar studies are under way in the glucocorticoid deficient rat. Studies are being conducted primarily to resolve the contributions of alteration in systemic hemodynamics and vasopressin release in the well established diluting disorder seen in this condition. Furthermore, the effect of alteration in arterial blood gases (pO2 and pCO2) on renal water excretion is being systematically investigated in both anesthetized and conscious animals. Both the afferent and the efferent pathways responsible for the antidiuresis associated with hypoxia and hypercapnia are being studied. The role of vasopressin, chemoreceptor and baroreceptors will be determined.